rs6779677

chr3-189741315-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003722.5(TP63):c.324+2541A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 151,928 control chromosomes in the GnomAD database, including 28,519 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (28519 hom., cov: 31)
• Consequence: TP63 NM_003722.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63

Genes affected

TP63 (HGNC:15979): (tumor protein p63) This gene encodes a member of the p53 family of transcription factors. The functional domains of p53 family proteins include an N-terminal transactivation domain, a central DNA-binding domain and an oligomerization domain. Alternative splicing of this gene and the use of alternative promoters results in multiple transcript variants encoding different isoforms that vary in their functional properties. These isoforms function during skin development and maintenance, adult stem/progenitor cell regulation, heart development and premature aging. Some isoforms have been found to protect the germline by eliminating oocytes or testicular germ cells that have suffered DNA damage. Mutations in this gene are associated with ectodermal dysplasia, and cleft lip/palate syndrome 3 (EEC3); split-hand/foot malformation 4 (SHFM4); ankyloblepharon-ectodermal defects-cleft lip/palate; ADULT syndrome (acro-dermato-ungual-lacrimal-tooth); limb-mammary syndrome; Rap-Hodgkin syndrome (RHS); and orofacial cleft 8. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TP63	NM_003722.5	c.324+2541A>C		intron_variant		ENST00000264731.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP63	ENST00000264731.8	c.324+2541A>C		intron_variant		1	NM_003722.5	P4

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92671 AN: 151810 Hom.: 28473 Cov.: 31

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.595

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.611 AC: 92779 AN: 151928 Hom.: 28519 Cov.: 31 AF XY: 0.612 AC XY: 45435 AN XY: 74242

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.778

Gnomad4 SAS AF: 0.661

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.593

Alfa AF: 0.594 Hom.: 18738

Bravo AF: 0.617

Asia WGS AF: 0.693 AC: 2411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.29
Dann	Benign	0.63

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6779677; hg19: chr3-189459104;